Genetic and hereditary influences that give rise to variation in the magnitude and direction of lateralization are presently the least understood processes in the etiology of cerebral dominance. Because the mice exhibit marked asymmetries that are analogous, if not prototypic to the expressed functional asymmetries of human beings, and because the knowledge of the genetics of the mouse is far more advanced than that of any other mammal, studies of the hereditary bases of lateralization in mice can make unique contributions to an understanding of lateralization of the nervous system. The objective of this research is to gain increased knowledge of the genetic, hereditary, developmental and neurobiological processes leading to the variability in the expression of brain/behavioral asymmetry in genetically defined and definable strains and stocks of mice. The long-term goal is to create and characterize practical experimental models of variable lateralization that will be useful for understanding normative processes as well as specific behavioral differences, deficits and associated pathology arising from anomalous patterns of lateralization in humans. A unique mammalian genetic resource for these studies is being developed following eleven generations of directional selective breeding. The HI and LO lines differ from each other in degree of asymmetry, as well as from intermediate lateralization expressed by the HET reference population. In addition, three panels of incipient inbred strains are being developed from the selected lines and their crosses to provide resources for studies of complex genetic-environment interactions. Specific research aims during the next project period are (a) to assess divergence between HI, LO, and HET control lines following 3 additional generations of reimpressed selections; (b) to continuously monitor degree of lateralization between lines; (c) to continue to develop the panel of incipient inbred strains derived for the HI, LO lines and their crosses; (d) to initiate genetic and behavioral characterization of these inbred strains; (e) to test the hypothesis that H-2 associated genes affect variable brain/behavioral asymmetry in experiments using panels of H-2 congenic mice; and (f) to actively pursue studies on the neurobiological mechanisms underlying the observed differences of brain/behavioral asymmetry through collaborative efforts with other neuroscientists who bring special expertise to the study of cerebral lateralization.